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Mesoporous Silica Nanoparticles Functionalized With Folic Acid and Zinc for Enhanced Targeted Delivery of Daunorubicin to Breast Cancer Cells Publisher Pubmed



Sheykholeslami S E ; Farsani N K ; Azari Incheh Sablagh Y ; Afshari Behbahanizadeh S ; Keshvadi M ; Najafi F ; Noorbazargan H
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Source: Scientific Reports Published:2026


Abstract

Targeted delivery of therapeutic agents may enhance anticancer efficacy through specific mechanisms. We have developed and characterized folic acid-functionalized mesoporous silica nanoparticles with co-loaded Daunorubicin and Zn2⁺ ions (FA-DAN-Zn/MSN), and we tested their anti-cancer activity in MCF-7 breast cancer cells. We characterized the nanoparticles and demonstrated a narrow size range with a negative zeta potential and spherical morphology (consistent with transmission electron microscopy (TEM)). Drug release titrations showed that the nanoparticles had pH-responsive properties by demonstrating preferential drug release at lower pH values, which would be consistent with a tumor microenvironment. Stability studies indicated that the nanoparticles remained stable under physiological conditions. The FA-DAN-Zn/MSN produced a more cytotoxic response to the MCF-7 cells in an MTT assay than free DAN, with no impact on the viability of the non-tumorigenic MCF-10A cells. Mechanistically, we showed that the FA-DAN-Zn/MSN included upregulation of pro-apoptotic markers (BAX and Caspase-9) and downregulation of the anti-apoptotic marker BCL-2, on their regulation with reduced markers of MMP-2 and MMP-9. Both reactive oxygen species (ROS) generation and caspase activity were consistent with inducible apoptosis, and the scratch assays indicated perturbation of cancer cell motility consistent with the idea of intervention. In summary, we recognize potential as a selective and efficacious nanocarrier for co-delivery and provide improved bioavailability and tumor target relative as compared to free drug treatment, which demonstrates further anticancer effects through enhanced apoptotic and anti-proliferative activity. © The Author(s) 2026.
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